Biology subjects

Valencia, J.

Publications and source records attributed to Valencia, J..

4 recordsLinked to original sources

bioRxiv2024

Generalists in a Specialist World: Vibrio-Phages with Broad Host Range

The host range of a bacteriophage--the diversity of hosts it can infect--is central to understanding phage ecology and applications. While most well-characterized phages have narrow host ranges, broad-host-range phages represent an intriguing component of marine ecosystems. The genetic and evolutionary mechanisms driving their generalism remain poorly understood. In this study, we analyzed Schizotequatroviruses and their Vibrio crassostreae hosts, collected from an oyster farm. Schizotequatroviruses exhibit broad host ranges, large genomes (~252 kbp) encoding 26 tRNAs, and conserved genomic organization interspersed with recombination hotspots. These recombination events, particularly in regions encoding receptor-binding proteins and antidefense systems, highlight their adaptability to host resistance. Notably, some lineages demonstrated receptor-switching between OmpK and LamB, showcasing their evolutionary flexibility. Despite their broad host range, Schizotequatroviruses were rare in the environment. Their scarcity could not be attributed to burst size, which was comparable to other phages in vitro, but may result from ecological constraints or fitness trade-offs, such as their preference for targeting generalist vibrios in seawater rather than the patho-phylotypes selected in oyster farms. Our findings clarify the genetic and ecological trade-offs shaping Schizotequatrovirus generalism and provide a foundation for future phage applications in aquaculture and beyond.

microbiology↗

bioRxiv2024

Rapid precision targeting of nanoparticles to lung via caveolae pumping system in endothelium

Modern medicine seeks precision targeting, imaging and therapy to maximize efficacy and avoid toxicities. Nanoparticles (NPs) have tremendous, yet unmet clinical potential to carry and deliver imaging and therapeutic agents systemically with tissue precision. But their size contributes to unwanted rapid scavenging by the reticulo-endothelial system (RES) and poor penetration of key endothelial cell (EC) barriers, both limiting target-tissue uptake, safety and efficacy. Here, we discover the extraordinary yet size-dependent ability of the EC caveolae pumping system (CPS) to deliver NPs rapidly and specifically into lungs. Gold and dendritic NPs are conjugated to aminopeptidase-P2 antibodies targeting caveolae of lung microvascular endothelium. SPECT-CT imaging and biodistribution analyses reveal that rat lungs extract most of the intravenously injected dose within minutes to achieve rapid blood clearance, high lung tissue concentrations well beyond peak blood levels, and precision lung imaging and targeting. Active transcytosis by caveolae greatly outperforms passive transvascular delivery and can even outpace RES scavenging. These results reveal how much ECs can both limit and promote tissue penetration of NPs and the power and limitations of the CPS. This study provides a new retargeting paradigm for small NPs to avoid RES uptake and achieve unprecedented rapid precision nanodelivery for future diagnostic and therapeutic applications.

bioengineering↗

bioRxiv2019

Distinct and shared contributions of diagnosis and symptom domains to cognitive performance in severe mental illness

BackgroundSevere mental illness (SMI) diagnoses display overlapping symptomatology and shared genetic risk, motivating trans-diagnostic investigations of disease-relevant quantitative measures. We analyzed relationships between neurocognitive performance, symptom domains, and diagnoses, in a large sample of SMI cases (ascertained agnostic to diagnosis) and healthy controls from a single, homogeneous population. Methods2,406 participants (1,689 cases, 717 controls; mean age 39 years, 64% female) were assessed for speed and accuracy using the Penn Computerized Neurocognitive Battery (CNB). Cases carried structured-interview based diagnoses of schizophrenia (SCZ, n=160), bipolar-I (BP-I, n=519), bipolar-II (BP-II, n=204) and major depressive disorder (MDD, n=806). Linear mixed models, using CNB tests as repeated measures, modeled neurocognition as a function of diagnosis, sex, and all interactions. Follow-up analyses, in cases, included symptom factor scores obtained from exploratory factor analysis of symptom data, as main effects. FindingsBP-I and SCZ displayed nearly identical impairments in accuracy and speed, across cognitive domains. BP-II and MDD performed similarly to controls, with subtle deficits in executive and social cognition. A three-factor model (psychosis, mania, and depression) best represented symptom data. Controlling for diagnosis, premorbid IQ, and disease severity, high lifetime psychosis scores were associated with reduced accuracy and speed across cognitive domains, while high depression scores were associated with increased social cognition accuracy. InterpretationTrans-diagnostic investigations demonstrated that neurocognitive function in SMI is characterized by two distinct profiles (BP-I/SCZ and BP-II/MDD), and is associated with specific symptom domains. These results suggest the utility of this design for elucidating SMI causes and trajectories.

neuroscience↗

bioRxiv2019

Drug related and psychopathological symptoms in HIV-positive men who have sex with men who inject drugs during sex (Slamsex): Data from the U-SEX GESIDA 9416 Study.

ObjectivesIntravenous sexualized drug use also known as slamsex seems to be increasing among HIV-positive men who have sex with men (MSM). This practice may entail severe consequences for physical and mental health in this population. Research on the subject is scarce. The aim of our study was to describe the psychopathological background of a sample of HIV positive MSM who practiced slamsex during the previous year and compare the physical and psychological symptoms between these participants and those who practiced sexualized drug use (SDU) or chemsex without slamsex.\n\nDesign and MethodsParticipants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional survey on sexual behaviour and recreational drug use. The present analysis is based on HIV-positive MSM who had practiced SDU.\n\nResultsThe survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) practiced chemsex, and of these, 34 (15.7%) had practiced slamsex. Participants who practiced slamsex were more likely to have current psychopathology (depression, anxiety and drug related disorders) than chemsex users. In addition, participants who practiced slamsex had more high-risk sexual behaviours, polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with patients who did not inject drugs, patients who engaged in slamsex showed more severe drug related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms related to SDU, such as paranoid thoughts and suicidal behaviour.\n\nConclusionSlamsex (intravenous SDU) is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.

scientific communication and education↗